PCT International publication No. WO89/04673 [Tokuhyo (Publication of the Translation of International Patent Application) 503315/1990] discloses a method of producing a solid polymer preparation wherein said solid preparation is kept at a temperature not lower than the glass transition point of the constituent polymer.
EPA No. 0586238 discloses a method of producing sustained-release microcapsules containing a biologically active substance from an W/O emulsion comprising an inner aqueous phase containing said biologically active substance and an external oil phase containing a biodegradable polymer, characterized in that microcapsules formed on microencapsulation of said biologically active substance with said biodegradable polymer heated at a temperature not lower than the glass transition temperature of said biodegradable polymer but not so high as to cause aggregation of the microcapsules.
With regard to sustained-release microcapsules incorporating a biodegradable polymer, it is desirable that the initial release of the bioactive substance, especially that in excess within 1 day, be suppressed, and that the release of the bioactive substance be optionally controlled over an extended period of time. However, the description in the above-mentioned patent publications does not enable the production of fully satisfactory sustained-release microcapsules that release the bioactive substance, especially polypeptide having a high molecular weight, at constant rate over an extended period of time from just after administration with suppressed initial release of the bioactive substance in excess just after administration.